Studies on the thyroid in transgenic mice expressing the genes for human and bovine growth hormone

The thyroid glands of transgenic mice (TM) expressing the genes for human (h) and bovine (b) growth hormone (GH) were studied. The percentages of larger follicles in hGH TM of either sex were significantly greater than in the corresponding normal littermates, and follicles ranging up to 350 microns in diameter were present in male hGH TM. In contrast, thyroid follicles were only slightly enlarged in male bGH TM, and were unchanged in female bGH TM. The serum concentrations of T4 were significantly decreased in male bGH TM and not altered in the other groups. Serum concentrations of T3 were slightly, but significantly increased in female hGH TM and female bGH TM, but were unaffected in male TM of either type. Since the principal difference between these foreign GHs in rodents is the additional lactogenic activity of human GH, these results may indicate that the effects of prolactin can influence the development of the thyroid.     

The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin

Summary 2 new limonoid-type terpenes have been isolated from an aqueous extract of seeds produced by the Eastern Himalayan (India) plantAphanamixis grandifolia Bl. By interpreting principally mass spectral and nuclear magnetic resonance data, the structures of 12-hydroxyamoorastatin (2b) and amoorastatone (3) were elucidated. Unequivocal evidence for the 12-hydroxyamoorastatin structural assignment was obtained by chemical conversion to sendanin (4). Amoorastatin derivative2b was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines but amoorastatone in the same system was inactive. In a comparative biological study, sendanin (4) and anthothecol (7) were also found significantly to inhibit growth of the P388 cell line, while rohitukin (8) and limonin (9) were found to be inactive.Part 63 of the series Antineoplastic Agents. For the previous contribution refer to G.R. Pettit, T.S. Krupa and R.M. Reynolds, Int. J. Peptide Protein Res., in preparation. The present investigation was supported in part by Public Health Research Grant No. CA-16049-05 from the National Cancer Institute, the Fannie E. Rippel Foundation, Mrs Mary Dell Pritzlaff, the Spencer T. and Ann W. Olin Foundation, Mr John F. Schmidt, and the Phoenix Coca-Cola Bottling Company.     

Chromosomal investigation ofCtenopharyngodon idella x Aristichthys nobilis hybrids

Summary Diploid, triploid, and gynogenetic offspring resulted from hybridizing femaleCtenopharyngodon idella with maleAristichthys nobilis.This research was supported in part by a contract with the Coachella Valley Water District, Coachella, California.     

Chemical defense in the three European species ofCrematogaster ants

The composition of the Dufour gland of the antC. scutellaris has been reinvestigated by gas chromatography/mass spectrometry. The major components of the gland are (2E,5E,12Z)-4-oxoheneicosa-2,5,12-trien-1-ol acetate (1a) its ¹⁴ and ¹⁶ double bond isomers (1b and1c), and the corresponding (Z,Z)-dienes5a and5b, all containing an acetylated C₂₁ chain. The previously proposed structures1d, 1e, and5c, which are based on an homologous acetylated C₂₃ chain, correspond to minor derivatives present in the gland. Traces of acetylated C₁₉ homologs, tentatively identified as1g-1i, have also been found. The Dufour gland contents of the two other EuropeanCrematogaster species have also been studied.C. auberti is very similar toC. scutellaris in producing mainly1a, 1b and1c, together with the same higher and lower homologs, but it lacks the dienic derivatives5, whereasC. sordidula contains essentially the acetylated C₁₉ compounds1g, 1h, and1i, accompanied by acetylated C₁₇ homologs.     

The isolation and structure of 13,18-dehydroglaucarubinone,a new antineoplastic quassinoid fromSimarouba amara

Summary An investigation of the Guyana plantSimarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.Antineoplastic agents 59. For part 58 refer to M. T. Edgar, G.R. Pettit and T.H. Smith, J. org. Chem., in preparation.Acknowledgments. We wish to thank Mr B. Septe for providing the¹³C-NMR-data. Dr Jean H. Schmidt and Miss Linda M. Lange for assistance with biological studies.—G.R. Pettit is grateful to the National Cancer Institute (performed pursuant to contract No. N01-67048 with the Division of Cancer Treatment, NCI, National Institutes of Health, Dept. of Health, Education and Welfare), Public Health Services Research grant No. CA 16049-03 from the National Cancer Institute, the Fannie E. Rippel Foundation, Talley Industries, and the Phoenix Coca-Cola Bottling Co., for partial support of this investigation.     

Juvenile hormone titre and regulation in the cockroachDiploptera punctata

Summary Titres of juvenile hormone (JH) have been determined in both hemolymph and whole body extracts of femaleDiploptera punctata during the first gonotrophic cycle using a method employing gas chromatography/mass spectrometry for qualitative and quantitative analysis. JH III is the sole JH found in both adult and last instarD. punctata. Maximum values of 1500 ng/ml (6M) were observed at the middle of the gonotrophic cycle, when basal oocyte growth rate was greatest. Changes in rates of JH release in vitro by corpora allata paralleled closely the changes in JH titre, suggesting that biosynthesis is a major regulator of titre. JH levels per animal were calculated from observed JH titres, and at certain time points in the gonotrophic cycle JH levels obtained from analysis of whole bodies were significantly greater than those predicted from hemolymph titres. These results suggest the existence of a nonhemolymph JH pool inD. punctata. Decay in JH titre after allatectomy of 5 day females has also been studied. Following a rapid initial decline, the rate of decay slowed appreciably 4 h post-operation. Thus, use of a first-order rate constant to estimate half-life of JH significantly underestimated the longevity of the hormone. The apparent persistence of JH following allatectomy may be due to the existence of a nonhemolymph JH pool.     

Sex pheromone of the pine sawflyDiprion pini (Hymenoptera: Diprionidae): Chemical identification,synthesis and biological activity

The main component of the sex pheromone secretion of femaleDiprion pini L. (Hymenoptera: Diprionidae) from insects collected both in Finland and in France has been identified as athreo-3,7-dimethyl-2-tridecanol (8 ng per female) stereoisomer by GC-MS and synthesis. The secretion also contains lower and higher homologues in small amounts (1–4% of the main component). Combined gas chromatographic-electroantennographic detection showed activity in both natural and esterified extracts (acetates and propionates); the esters of the main component gave the largest responses. The acetates and propionates of the eight stereoisomers of 3,7-dimethyl-2-tridecanol were synthesized from enantiomerically highly enriched (>99% ee) building blocks. The stereochemistry of the main component was established to be (2S,3R,7R)-3,7-dimethyl-2-tridecanol by GC analysis of the natural material. It was purified by liquid chromatography prior to the GC analysis of both its pentafluorobenzoates and its isopropylcarbamates on a non-chiral polar column (ECD) and a chiral column (NPD), respectively. Field tests demonstrated that both the acetate and propionate of the main component (100 g of each applied on cotton roll dispensers) were active in attracting males, with or without the presence of several of the minor compounds. Experiments with smaller amounts of the acetate and the propionate (1 g in France and 50 g in Finland) demonstrated that the propionate was more active than the acetate, and that it also caught more males than a blend of the two compounds.     

Laboratory and field studies of the female sex pheromone of the olive moth,Prays oleae

Summary Analysis by GC-EAG indicates that abdominal tip extracts of femalePrays oleae contain a tetradecenal. Synthetic (Z)-7-tetradecenal elicits a strong EAG respones from maleP. oleae and field tests it to be comparable in attractancy with the virgin female moth. (Z)-9-Tetradecenal also produces a strong EAG response but it is not an attractant and, when added to (Z)-7-tetradecenal, markedly reduces trap catches.Acknowledgments. The authors are indebted to Mr N. Psylakis, Agricultural Research Centre, Chania, Crete, and to Dr D. Vassilopoulos, Benaki Phytopathological Institute, for providing facilities for this work. They thank the Commonwealth Institute of Entomology, London, for moth species confirmation.     

Histopathological effect of thiourea on the ovarian tissues ofSarcophaga ruficornis (Fabr.)

Summary The primary target of thiourea in femaleSarcophaga are the follicles in the ovarioles. The follicle cells as a result become syncytial and their nuclei get pycnotic, inhibiting the transport of nutrient material into the nurse cells and of yolk into the oocytes. The subnormal eggs produced are not viable.     

(Z)-9-tetradecen-1-ol and (Z)-9-tetradecenyl acetate: A potent attractant system for maleSesamia cretica Led. (Lep., Noctuidae)

Summary Field studies have shown that a combination of (Z)-9-tetradecenol with (Z)-9-tetradecenyl acetate is an effective attractant for maleSesamia cretica Led., a pest of sorghum crops. These studies also indicated that the most effective composition is 7525 (alcohol:acetate).We thank Dr E. Berio for the insect determination.     

A new tryptophan derived alkaloid fromEvodia rutaecarpa (Juss.) Benth. et Hook

Summary The first tryptophan-derived indolopyridoquinazoline alkaloid has been isolated from the fruits ofEvodia rutaecarpa (Jussieu) Bentham et Hook. Its structure is deduced on the basis of spectral data and enantioselective synthesis. The compound has been assigned the absolute configuration (7S,13bS)-7-carboxy-8,13,13b,14-tetrahydro-14-methylindolo[2,33,4]pyrido[2,1-b]quinazolin-5(7H)-one.     

The action of iodoacetate on the antigenic power of insulin

Résumé Nous avons observé que le iodoacétate en concentrations de 1·10^–4, 5 · 10^–5 et 1 · 10^–5 M et préalablement incubé à 37 °C, a une influence de l'ordre de 61, 50 et 44% respectivement sur la totalité du pouvoir antigénique de l'insuline de buf. L'effet inhibitif est proportionnel à la durée d'incubation et l'on ne constate pas de différences lorsque les concentrations de l'hormone se trouvent entre 100 et 300U/ml.     

Dissection of the pheromone-modulated flight of moths using single-pulse response as a template

The upwind flight of male moths to conspecific females is mediated by the chemical and structural characteristics of a pheromone plume. We describe the reaction of maleCadra cautella, the almond moth, to the interception of single pulses of sex pheromone, the smallest structural units of odour plumes. Following loss of a pheromone plume, males cast, that is fly a crosswind course without progressing upwind. The response of casting males to interception of a pulse of 0.25 s duration was, after a delay of 0.21±0.07 s, to turn and briefly fly straighter upwind, resulting in average net upwind displacements of 18 cm in a 50 cm s^–1 wind. Upwind progress in the single-pulse response was the result of steering more upwind and an increase in airspeed, although average ground speed remained unchanged. During the last third of the surge, males turned crosswind, returning to casting flight. These behavioural reactions to pheromone contact and loss support the phasic-tonic model of odour-modulated flight, in which an underlying tonic counterturning rhythm, expressed upon pheromone loss, is briefly overridden by phasic upwind surges, expressed upon interception of the pheromone filament. The surge portion of the cast-surge-cast response was diminished and more crosswind if individual pulses were shorter (0.02 s), probably due to sub-optimal contact with pheromone. The cast-surge-cast response to interception of a single 0.25 s pulse was used as a template to interpret the form of flight tracks in plumes of known structure. The template matched portions of flight tracks of males flying in plumes of low pheromone pulse frequency, thus reflecting the male's pattern of pulse encounter. In plumes ensuring a high frequency of pulse interception, only the upwind surge portion of the template was expressed, resulting in nearly straight upwind flight tracks. Similar nearly straight upwind flight tracks occurred in flights along plumes of low pulse frequency with large volume. Thus flight tracks of maleC. cautella to point sources of pheromone depend on both the frequency and the size of filaments encountered.     

Molecular characterization of <Emphasis Type="Italic">Arabidopsis</Emphasis> PHO80-like proteins,a novel class of CDKA;1-interacting cyclins

Cyclins are regulatory proteins that interact with cyclin-dependent kinases (CDKs) to control progression through the cell cycle. In Arabidopsis thaliana, 34 cyclin genes have been described, grouped into five different types (A, B, D, H, and T). A novel class of seven cyclins was isolated and characterized in Arabidopsis, designated P-type cyclins (CYCPs). They all share a conserved central region of 100 amino acids (cyclin box) displaying homology to the corresponding region of the PHO80 cyclin from Saccharomyces cerevisiae and the related G1 cyclins from Trypanosoma cruzi and T. brucei. The CYCP4;2 gene was able to partially re-establish the phosphate-dependent expression of the PHO5 gene in a pho80 mutant strain of yeast. The CYCPs interact preferentially with CDKA;1 in vivo and in vitro as shown by yeast two-hybrid analysis and co-immunoprecipitation experiments. P-type cyclins were mostly expressed in proliferating cells, albeit also in differentiating and mature tissues. The possible role of CYCPs in linking cell division, cell differentiation, and the nutritional status of the cell is discussed.Received 9 February 2004; received after revision 18 March; accepted 19 April 2004     

The metabolism of the male antifertility agent 1-amino-3-chloropropan-2-ol in the rat

Summary The male antifertility agent 1-amino-3-chloropropan-2-ol (ACP,I) has been shown to be metabolized to-chlorohydrin (III) and metabolites of-chlorohydrin. This accounts for the similar antifertility and renal toxicity effects of both compounds.     

Spruce budworm: Effects of different blends of sex pheromone components on disruption of male attraction

Summary Disruption of attraction of maleChoristoneura fumiferana to the natural sex pheromone in an atmosphere permeated by blends of the 2 pheromone components is greatest with ratios of the 2 components close to the natural blend.The (E)- and (Z)-TDALs were obtained from ChemSampCo, Columbus, Ohio, and were further purified by argentation column chromatography on Hi-Flosil-Ag (20% AgNo₃), 60/200 mesh, eluting with 91 pentane: ether. Following formulation, (E)(Z) ratios in the PVC were determined by extracting PVC pellets for 6 h in hexane and analyzing the solvent by GLC. The chemical analyses and purifications were carried out by Ms Linda MacDonald of the Forest Pest Management Institute, Sault Ste. Marie, Ont., to whom I would like to express my thanks.Analyses of the data were done with the help of Dr J. Régnière of the Great Lakes Forest Research Centre, Sault Ste. Marie, Ont. whom I would also like to thank.     

Experimental immunity against trypanosomiasis

Summary 9 groups of 6 female rats were used in an experiment using fraction 3 ofTrypanosoma rhodesiense. 500 g gave 100% immunoprotection and 1000 and 1500 g gave 66% immunoprotection when challenged with 5×10² T. brucei. 2 groups of 10 female rats were tested for a short period inoculation immune response. In this, 750 g of fraction 3 ofT. rhodesiense gave 70% immunoprotection when challenged withT. brucei.I thank the University of Zambia for support; Dr M. A. Q. Awan, Mazabuka, Zambia, forT. rhodesiense andT. brucei; Prof. J. W. Kibukamusoke, Dr O. Okong'o and Dr W. W. Anokbonggo for advice; Mr L. Nyaliti for technical help.     

Effect of 3,5,3′-tri-iodothyronine on cellular growth and oxygen consumption in neonatal rat brain

Summary The effect of thyroid deficiency and treatment with tri-iodothyronine (T₃) on oxygen consumption by neonatal (6-day-old and 15-day-old) rat brain was examined using glutamate, -hydroxybutyrate, succinate and ascorbate+TMPD as substrates. The respiration rates decreased significantly in 15-day-old hypothyroid pups. Treatment of normal and of hypothyroid pups with T₃ resulted in a significant increase in the respiration rate at both ages. Respiration rates with glucose as the substrate were not affected under these conditions.     

Changes in dopamineβ-hydroxylase activity of monkey plasma with age

Summary Plasma dopamine -hydroxylase activity of Japanese monkeys (Macaca fuscata fuscata) increased with age, and the developmental changes were similar to those of human beings. However, the adult level plasma DBH activity of various monkey species was much lower than that of human beings.We thank Dr.K. Nozawa, Dr.O. Takenaka and Mr.T. Shotake (Primate Research Institute, Kyoto University) for their help in collecting monkey blood samples.     

The identity of vincamajoridine and akuammine

Résumé Les auteurs démontrent que la vincamajoridine C₂₂H₂₆O₄N₂; F. 258; ()_D-104±4° (py) récemment extraite de la Grande Pervenche (Vinca major L.) est identique à l'akuammine antérieurement découverte dans les graines d'une autre ApocynacéePicralima nitida (Stapf) T. etH. Durand.